Asymptomatic Trasmission, the Achilles'Heel of Current Strategies to Control Covid-19

1. Edi t or i a l
The new engl and jour nal of medicine
n engl j med nejm.org 1
Asymptomatic Transmission, the Achilles’ Heel
of Current Strategies to Control Covid-19
Monica Gandhi, M.D., M.P.H., Deborah S. Yokoe, M.D., M.P.H., and Diane V. Havlir, M.D.
Traditional infection-control and public health
strategies rely heavily on early detection of dis-
ease to contain spread. When Covid-19 burst onto
the global scene, public health officials initially
deployed interventions that were used to control
severe acute respiratory syndrome (SARS) in 2003,
including symptom-based case detection and
subsequent testing to guide isolation and quar-
antine. This initial approach was justified by the
many similarities between SARS-CoV-1 and SARS-
CoV-2, including high genetic relatedness, trans-
mission primarily through respiratory droplets,
and the frequency of lower respiratory symptoms
(fever, cough, and shortness of breath) with both
infections developing a median of 5 days after ex-
posure. However, despite the deployment of simi-
lar control interventions, the trajectories of the
two epidemics have veered in dramatically differ-
ent directions. Within 8 months, SARS was con-
trolled after SARS-CoV-1 had infected approxi-
mately 8100 persons in limited geographic areas.
Within 5 months, SARS-CoV-2 has infected more
than 2.6 million people and continues to spread
rapidly around the world.
What explains these differences in transmis-
sion and spread? A key factor in the transmissi-
bility of Covid-19 is the high level of SARS-CoV-2
shedding in the upper respiratory tract,1
even
among presymptomatic patients, which distin-
guishes it from SARS-CoV-1, where replication
occurs mainly in the lower respiratory tract.2
Viral loads with SARS-CoV-1, which are associat-
ed with symptom onset, peak a median of 5 days
later than viral loads with SARS-CoV-2, which
makes symptom-based detection of infection more
effective in the case of SARS CoV-1.3
With influ-
enza, persons with asymptomatic disease gener-
ally have lower quantitative viral loads in secretions
from the upper respiratory tract than from the
lower respiratory tract and a shorter duration of
viral shedding than persons with symptoms,4
which decreases the risk of transmission from
paucisymptomatic persons (i.e., those with few
symptoms).
Arons et al. now report in the Journal an out-
break of Covid-19 in a skilled nursing facility in
Washington State where a health care provider
who was working while symptomatic tested posi-
tive for infection with SARS-CoV-2 on March 1,
2020.5
Residents of the facility were then offered
two facility-wide point-prevalence screenings for
SARS-CoV-2 by real-time reverse-transcriptase
polymerase chain reaction (rRT-PCR) of nasopha-
ryngeal swabs on March 13 and March 19–20,
along with collection of information on symptoms
the residents recalled having had over the pre-
ceding 14 days. Symptoms were classified into
typical (fever, cough, and shortness of breath),
atypical, and none. Among 76 residents in the
point-prevalence surveys, 48 (63%) had positive
rRT-PCR results, with 27 (56%) essentially asymp-
tomatic, although symptoms subsequently devel-
oped in 24 of these residents (within a median
of 4 days) and they were reclassified as presymp-
tomatic. Quantitative SARS-CoV-2 viral loads were
similarly high in the four symptom groups (resi-
dents with typical symptoms, those with atypical
symptoms, those who were presymptomatic, and
those who remained asymptomatic). It is notable
that 17 of 24 specimens (71%) from presymptom-
atic persons had viable virus by culture 1 to 6 days
before the development of symptoms. Finally, the
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2. The new engl and jour nal of medicine
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mortality from Covid-19 in this facility was high;
of 57 residents who tested positive, 15 (26%) died.
An important finding of this report is that
more than half the residents of this skilled nurs-
ing facility (27 of 48) who had positive tests were
asymptomatic at testing. Moreover, live corona-
virus clearly sheds at high concentrations from
the nasal cavity even before symptom develop-
ment. Although the investigators were not able to
retrospectively elucidate specific person-to-person
transmission events and although symptom as-
certainment may be unreliable in a group in
which more than half the residents had cogni-
tive impairment, these results indicate that as-
ymptomatic persons are playing a major role in
the transmission of SARS-CoV-2. Symptom-based
screening alone failed to detect a high proportion
of infectious cases and was not enough to control
transmission in this setting. The high mortality
(>25%) argues that we need to change our cur-
rent approach for skilled nursing facilities in
order to protect vulnerable, enclosed populations
until other preventive measures, such as a vaccine
or chemoprophylaxis, are available.
A new approach that expands Covid-19 test-
ing to include asymptomatic persons residing or
working in skilled nursing facilities needs to be
implemented now. Despite “lockdowns” in these
facilities, coronavirus outbreaks continue to
spread, with 1 in 10 nursing homes in the United
States (>1300 skilled nursing facilities) now re-
porting cases, with the likelihood of thousands of
deaths.6
Mass testing of the residents in skilled
nursing facilities will allow appropriate isolation
of infected residents so that they can be cared
for and quarantine of exposed residents to mini-
mize the risk of spread. Mass testing in these
facilities could also allow cohorting7
and some
resumption of group activities in a nonoutbreak
setting. Routine rRT-PCR testing in addition to
symptomatic screening of new residents before
entry, conservative guidelines for discontinuation
of isolation,7
and periodic retesting of long-term
residents, as well as both periodic rRT-PCR screen-
ing and surgical masking of all staff, are important
concomitant measures.
There are approximately 1.3 million Americans
currently residing in nursing homes.8
Although
this recommendation for mass testing in skilled
nursing facilities could be initially rolled out in
geographic areas with high rates of community
Covid-19 transmission, an argument can be made
to extend this recommendation to all U.S.-based
skilled nursing facilities now because case ascer-
tainment is uneven and incomplete and because
of the devastating consequences of outbreaks.
Immediately enforceable alternatives to mass test-
ing in skilled nursing facilities are few. The public
health director of Los Angeles has recommended
that families remove their loved ones from nurs-
ing homes,9
a measure that is not feasible for
many families.
Asymptomatic transmission of SARS-CoV-2
is the Achilles’ heel of Covid-19 pandemic control
through the public health strategies we have cur-
rently deployed. Symptom-based screening has
utility, but epidemiologic evaluations of Covid-19
outbreaks within skilled nursing facilities such
as the one described by Arons et al. strongly dem-
onstrate that our current approaches are inade-
quate. This recommendation for SARS-CoV-2 test-
ing of asymptomatic persons in skilled nursing
facilities should most likely be expanded to other
congregate living situations, such as prisons and
jails (where outbreaks in the United States, whose
incarceration rate is much higher than rates in
other countries, are increasing), enclosed mental
health facilities, and homeless shelters, and to
hospitalized inpatients. Current U.S. testing ca-
pability must increase immediately for this strat-
egy to be implemented.
Ultimately, the rapid spread of Covid-19 across
the United States and the globe, the clear evi-
dence of SARS-CoV-2 transmission from asymp-
tomatic persons,5
and the eventual need to relax
current social distancing practices argue for
broadened SARS-CoV-2 testing to include asymp-
tomatic persons in prioritized settings. These
factors also support the case for the general pub-
lic to use face masks10
when in crowded outdoor
or indoor spaces. This unprecedented pandemic
calls for unprecedented measures to achieve its
ultimate defeat.
Disclosure forms provided by the authors are available with
the full text of this editorial at NEJM.org.
From the Department of Medicine, University of California, San
Francisco.
This editorial was published on April 24, 2020, at NEJM.org.
1. Wölfel R, Corman VM, Guggemos W, et al. Virological as-
sessment of hospitalized patients with COVID-2019. Nature
2020 April 1 (Epub ahead of print).
2. Cheng PK, Wong DA, Tong LK, et al. Viral shedding patterns
of coronavirus in patients with probable severe acute respiratory
syndrome. Lancet 2004;​363:​1699-700.
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3. Editorial
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3. To KK-W, Tsang OT-Y, Leung W-S, et al. Temporal profiles of
viral load in posterior oropharyngeal saliva samples and serum
antibody responses during infection by SARS-CoV-2: an observa-
tional cohort study. Lancet Infect Dis 2020 March 23 (Epub
ahead of print).
4. Ip DKM, Lau LLH, Leung NHL, et al. Viral shedding and
transmission potential of asymptomatic and paucisymptomatic
influenza virus infections in the community. Clin Infect Dis
2017;​64:​736-42.
5. Arons MM, Hatfield KM, Reddy SC, et al. Presymptomatic
SARS-CoV-2 infections and transmission in a skilled nursing
facility. N Engl J Med. DOI:​10.1056/NEJMoa2008457.
6. Cenziper D, Jacobs J, Mulcahy S. Nearly 1 in 10 nursing
homes nationwide report coronavirus cases. Washington Post.
April 20, 2020 (https://www​.washingtonpost​.com/​business/​
2020/​04/​20/​nearly​-­one​-­10​-­nursing​-­homes​-­nationwide​-­report​
-­coronavirus​-­outbreaks/​).
7. Centers for Disease Control and Prevention. Key strategies
to prepare for COVID-19 in long-term care facilities (LTCFs):​
updated interim guidance. April 15, 2020 (https://www​.cdc​.gov/​
coronavirus/​2019​-­ncov/​hcp/​long​-­term​-­care​.html).
8. Centers for Disease Control and Prevention. Nursing home
care. March 11, 2016 (https://www​.cdc​.gov/​nchs/​fastats/​nursing​
-­home​-­care​.htm).
9. Dolan J, Hamilton M. Consider pulling residents from nurs-
ing homes over coronavirus, says county health director. Los An-
geles Times. April 7, 2020 (https://www​.latimes​.com/​california/​
story/​2020​-­04​-­07/​coronavirus​-­nursing​-­homes​-­residents​-­remove​
-­la​-­county).
10. Centers for Disease Control and Prevention. Use of cloth face
coverings to help slow the spread of COVID-19. April 3, 2020
(https://www​.cdc​.gov/​coronavirus/​2019​-­ncov/​prevent​-­getting​-­sick/​
cloth​-­face​-­cover​.html).
DOI: 10.1056/NEJMe2009758
Copyright © 2020 Massachusetts Medical Society.
The New England Journal of Medicine
Downloaded from nejm.org by ROD STER on April 24, 2020. For personal use only. No other uses without permission.
Copyright © 2020 Massachusetts Medical Society. All rights reserved.